tbuckley/cabot-search huggingface dataset:
Abstract 10312: Meta-Analysis of Influenza Vaccine and Cardiovascular Outcomes
Authors: Ahmad Al-Abdouh, Waiel Abusnina, Mohammed Mhanna, ahmad jabri, Anan Abu Rmilah, Taha Ahmed, Taqwa Alabduh, Mostafa Zaalouk, Erin D Michos
Journal: Circulation (2022)

Introduction: Influenza infection is associated with increased cardiovascular morbidity and mortality. Many observational and clinical trials suggested that influenza vaccine can reduce cardiovascular outcomes. Methods: We searched EMBASE, PubMed, and Cochrane Library (inception through May 24th, 2022) for randomized controlled trials (RCTs) evaluating influenza vaccine and its association with cardiovascular outcomes. We used Mantel-Haenszel method with Paule-Mandel estimator of tau2 and Hartung-Knapp-Sidik-Jonkman adjustment (due to the small number of the included studies) to calculate the risk ratio (RR) and 95% confidence interval (CI). Results: Eight RCTs with a total of 14,420 patients were included in our analysis. Influenza vaccine as compared with control/placebo was associated with significantly lower risk of major adverse cardiovascular events (MACE) at follow-up [RR: 0.75; 95%CI: 0.57; 0.97; I2:56%] [Figure]. There was no significant difference between influenza vaccine and placebo/control in terms of all-cause mortality [RR: 0.84; 95%CI: 0.54; 1.33; I2:50%], cardiovascular mortality [RR: 0.77; 95%CI: 0.39; 1.50; I2:57%], or myocardial infarction [RR: 0.75; 95%CI: 0.52; 1.10; I2:0%]. Conclusion: Our meta-analysis suggests that influenza vaccine compared with control/placebo was associated with lower rates of MACE without a significant difference in the mortality or myocardial infarction rates.
Abstract 10897: Severe Atrial Dysfunction and Sick Sinus Syndrome in a Patient With Scn5a Mutation
Authors: Cristina Font, Tiffany Ho, Estelle Torbey
Journal: Circulation (2022)

Introduction: SCN5A mutations are associated with numerous cardiovascular conditions, including dilated cardiomyopathy, atrial fibrillation, and sick sinus syndrome. Specific variants in patients with severe atrial dysfunction may be associated with increased risk of stroke even in young patients. Case: This case describes a previously healthy 38-year-old male of French descent who presented with intermittent palpitations and presyncope associated with atrial flutter followed by prolonged conversion pauses up to 7.5 seconds, then followed by junctional bradycardia. Echocardiogram showed a mildly dilated left atrium. Electrophysiology study demonstrated extensive scarring in the left atrium with normal sinus node function and right atrial voltage. No atrial fibrillation was noted. He was also found to have typical atrial flutter and mitral flutter. He underwent cavotricuspid isthmus ablation and mitral annular flutter ablation. Due to his vagal-mediated pauses and junctional rhythm, he also underwent cardioneuroablation aimed at partial denervation. Following this, he had further episodes of junctional rhythm on the days after exercise. He underwent further total cardioneuroablation and was found to have progressive scarring at the sinus node area and sinus node dysfunction, so a permanent pacemaker was placed. He underwent genetic testing which demonstrated SCN5A heterozygous missense pathogenic variant c.2823G&gt;A. Conclusion: The SCN5a gene encodes the alpha subunit of the cardiac sodium channel, which is responsible for initiation and propagation of action potentials. SCN5A variants are associated with a number of cardiovascular conditions. There are reports of stroke in young French patients with severe atrial dysfunction and SCN5A mutations, including variant c.2823G&gt;A, demonstrating that severe atrial dysfunction is a risk factor for stroke regardless of CHADS2VASc score, and specific SCN5A mutations may be associated with increased risk of stroke. Given these reports and absence of relevant guidelines, apixaban was continued indefinitely for prevention of stroke. At follow-up two months later, the patient resumed physical activity and reported symptomatic improvement, without any episodes of syncope or near syncope.
Abstract 11000: Deep Learning Prediction of New-Onset Atrial Fibrillation Using Echocardiography Videos
Authors: Alvaro E Ulloa Cerna, Sushravya Raghunath, David vanMaanen, Jeffrey Ruhl, Brandon Fornwalt, John Pfeifer, Christopher M Haggerty
Journal: Circulation (2022)

Introduction: Patients at high risk of undiagnosed Atrial Fibrillation (AF) can be identified from 12-lead ECG and routed to increased monitoring via wearable devices such as a watch or an ECG patch. A similar prediction task may be feasible employing echocardiography, increasing the likelihood of detecting patients at high risk for AF. Hypothesis: We hypothesized that by leveraging a large echocardiography database, a model can be trained to accurately predict future AF onset in patients undergoing routine echocardiography. Methods: We collected data on patients with an echo at Geisinger (769,854 studies from 337,388 patients) and randomly grouped patients into training (80%) or testing (20%) sets. In the training cohort, studies were considered positive if they were obtained from patients with prior or new (&lt;1 year) AF diagnosis. Alternatively, negative studies were those obtained from AF-free patients (&gt;1 year). For testing, we selected one random echo per patient and restricted the positives to patients without prior AF diagnosis or new AF within 7 days of the echo. This was to avoid predicting positive AF at the time of echo. We tested the model on 38,808 valid studies where 5% developed AF within a year. We trained six convolutional neural networks, one per view (apical two, four and five chambers, basal and mid short-axis, and parasternal long-axis), and combined their outputs to train an XGboost model. Results: Among the six views, the apical four chamber yielded the best performance with an area under the ROC curve (AUROC) of 76%, followed by the apical two chamber with 65%, the apical five chamber with 58%, the parasternal long-axis with 57%, the basal short-axis with 56%, and the mid short-axis with 50%. A model combining all six planes yielded a 78% AUROC. Conclusions: CNN models trained on echocardiography videos can predict new-onset AF with moderate performance. We also found that views that captured the left atrium had better performance compared to those that did not.
Abstract 10917: Bone Mineral Density for Stratification and Prediction of Risk for Cardiovascular Outcomes in Women
Authors: Sarath lal Mannumbeth renjithlal, Mohamed Eid, Mostafa Zaalouk, Nikita Nand, Muhammad Ahmed Malik, Fahd Shaukat, Nathan Ritter, Amgad Makaryus, PILLAI NISHA
Journal: Circulation (2022)

Introduction: Atherosclerotic Cardiovascular disease ( ASCVD) in women remains understudied, under-diagnosed, and under-treated. It is known that traditional risk factors have varied effects on men's vs. women's hearts. However, the current risk stratification tools tend to underestimate or not consider such sex-specific factors. We aimed to investigate the utility of bone mineral density (BMD) with DEXA scoring as a predictor of ASCVD in women. Methods: Patients who underwent DEXA scanning from 2012 to 2014 at multiple centers within our health system were collected and categorized using International Classification of Diseases (ICD) diagnosis codes to identify comorbidities and outcomes. Age, Sex, Race, history of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), body mass index (BMI), and smoking status were noted. Results: Of the 2,254 patients who underwent DEXA scanning, 1,995 participants were female (88.5%), and 1,929 were white (85.6%) with an average age of 72.8 years. The primary outcome was any ASCVD event (stroke, MI and cardiac death). During the mean follow-up of 9 years, 245 patients (10.8%) experienced ASCVD events. Patients with osteoporosis defined by a T score &lt;-2.5 had higher odds of ASCVD events (OR - 3.82 [2.370-6.172], P&lt;0.0001). Osteopenia was defined by a T score between -1 and -2.5 and was not associated with an increased risk of ASCVD events (OR 1.2 [0.782-1.957] P &lt;0.36). Conclusions: BMD measurement with DEXA scanning may be useful for the stratification and prediction of risk for ASCVD events in women, with no additional economic strain on the healthcare system. Further wide-scale studies are needed to utilize this potentially promising predictor and commonly used diagnostic test. .
Abstract 10538: Metabolite Profiling Highlights Links Between Healthy Diet and Greater Cardiorespiratory Fitness in the Community
Authors: Michael Y Mi, Priya Gajjar, Maura E Walker, Vanessa Xanthakis, Martin G Larson, Ramachandran S Vasan, Ravi V Shah, Gregory D Lewis, Matthew Nayor
Journal: Circulation (2022)

Introduction: Cardiorespiratory fitness (CRF) is a powerful predictor of health outcomes, but its determinants are incompletely understood at the population level. Prior studies have suggested associations between dietary components and CRF, but they have generally been limited by small sample sizes, reliance on estimated CRF, variable dietary instruments, and lack of molecular interrogation to support shared biology. Hypothesis: Shared metabolite associations across dietary quality and CRF will prioritize metabolites potentially responsible for linking dietary quality with improved CRF in the community. Methods: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for quantification of CRF by peak oxygen uptake (VO 2 ) and completed food frequency questionnaires at a routine study visit. Dietary quality was assessed by the Mediterranean-style Diet Score (MDS), and fasting levels of 201 metabolites were quantified. Results: In 2380 FHS participants (age 54 ± 9 years, 54% women, BMI 28 ± 5 kg/m 2 ), a 1-SD higher MDS was associated with 4.4% (3.5% - 5.3%, p &lt; 0.0001) greater peak VO 2 in linear models adjusted for age, sex, cardiovascular risk factors, and physical activity. In a representative subsample that had metabolite profiling (N = 1154), 80 metabolites were statistically significantly associated with MDS, 57 with peak VO 2 , and 27 with both MDS and peak VO 2 in multivariable linear models (FDR &lt; 5% for all, Figure). These metabolites included dimethylguanidino valeric acid, medium chain acylcarnitines, and C16 ceramide, which are markers of insulin resistance and increased risk for cardiovascular disease. Metabolites with less established functions include C38:7 plasmalogens, which correlate with fish intake and may have anti-inflammatory effects. Conclusions: Healthy diet is associated with greater CRF in the community and may be partially explained by favorable metabolic health.
Abstract 10294: Center Level Factors Associated With Improved Length of Stay Following Stage 1 Palliation: An Analysis of the NPC-QIC Registry
Authors: Henry Foote, Dylan Thibault, Carla Dominguez Gonzalez, Garick D Hill, Luann Minich, Andrew McCrary, Kevin D Hill
Journal: Circulation (2022)

Introduction: Stage 1 single ventricle palliation has the longest associated length of stay (LOS) of STS benchmark operations. Patient level factors that contribute to prolonged hospitalization have been identified, but center level factors have not been explored. We aim to identify center level factors that drive post-Stage 1 palliation LOS. Methods: We analyzed data prospectively collected by the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry. We included all infants who underwent stage 1 followed by either stage 2 or death. We excluded centers with fewer than 10 cases and centers or patients with missing key variables. Our primary outcome was center level LOS. We grouped centers into quartiles based on median LOS for all patients at each center and compared patient and center level characteristics between highest and lowest performing quartiles using univariable analyses. Results: Of 2510 infants (65 sites), 1831 (30 sites) met study criteria (61% male, 61% white, 17% premature, 73% with hypoplastic left heart as primary cardiac diagnosis). There was wide inter-center variation in LOS (1st quartile centers: median 28 days [IQR 19, 47]; 4th quartile: 62 days [35, 96], p&lt;0.001). Shorter LOS correlated with more outside hospital days alive prior to stage 2, after accounting for readmissions (correlation coefficient -0.49, p&lt;0.001). Compared to 7 low performing centers, 8 high performing centers were more likely to perform the Norwood with an RV-PA conduit (64% v 48%, p&lt;0.001), extubate patients earlier (10 days [7, 15] v 14 days [11, 25], p&lt;0.001), start enteral feeds sooner (9 days [7, 13] v 13 days [10, 22], p&lt;0.001), and were more likely to discharge patients on nasogastric feeds (57% v 19%, p&lt;0.001) vs G-tube feeds (7% v 41%, p&lt;0.001) (Table 1). Conclusions: There was significant inter-center variation in post-Stage 1 LOS. Modifiable center-level practices may be targets to standardize practice and reduce overall LOS across centers.
Abstract 105: High-dose Intranasal Insulin In A Dose-escalation Study For Healthy Human Subjects
Authors: Florian F Schmitzberger, Jennifer Fowler, Cindy H Hsu, Manjunath Pai, Robert W Neumar, William J Meurer, Robert Silbergleit
Journal: Circulation (2022)

Introduction: Intranasal insulin is a putative neuroprotective therapy that could be easily delivered very early after cardiac arrest, but safety at doses extrapolated from animal models have not been studied in humans. We hypothesized that high-dose intranasal insulin can be safely delivered to healthy human subjects. Methods: This was a phase 1, open label dose-finding study of intranasal insulin in healthy participants.The primary objective was to determine the maximum tolerated dose of intranasal insulin in healthy subjects. Placebo and insulin were given intranasally to supine healthy volunteers intranasally at escalating doses from 0 to 1000 units on repeated weekly visits. Serum glucose, insulin, and C-peptide levels were measured serially at 0, 15, 30, 60, 120, 180 and 240 minutes after administration. Results: Twenty four participants (12 female, median age 53.5, IQR 35.75-61) were enrolled. There was no change in average serum glucose after administration of intranasal insulin. Average serum insulin increased slightly in a dose-dependent manner, peaking at 15 minutes. C-peptide went down over time from administration in all groups. One participant had severe hypoglycemia (minimum 24 mg/dL 45 min after receiving 600U intranasal insulin) that was corrected with oral intake and intravenous dextrose. Another participant had transient hypoglycemia (minimum 51 mg/dL at 30 min) also after 600U intranasal insulin with mild symptoms that was corrected with oral intake. Hypoglycemic episodes were associated with increases in serum insulin. Both participants continued in the study without hypoglycemia after additional doses. One participant dropped out for reasons unrelated to the intervention. Discussion: High-dose intranasal insulin up to 1000U was well tolerated, without changes in mean glucose, but with small measurable systemic absorption. Idiosyncratic hypoglycemia requires further study. Delivery of intranasal insulin to the brain at these doses, and efficacy of high-dose intranasal insulin as a neuroprotective therapy after cardiac arrest require further study.
Abstract 10214: Invasive versus Echocardiographic Hemodynamics in the First Genetically Modified Porcine to Human Xenotransplant
Authors: Cullen Soares, Susie N Hong, Peter Hanna, Corbin E Goerlich, Charles C Hong, Timm Dickfeld, Alison Grazioli, Muhammad Mohiuddin, Bartley Griffith, Manjula Ananthram
Journal: Circulation (2022)

Introduction: Our medical center performed the first genetically modified cardiac xenotransplant in human and performed longitudinal invasive and noninvasive hemodynamic measurements throughout the recipient’s hospitalization. We hypothesized that echocardiographic derived hemodynamic assessments would correlate with invasive measurements within the cardiac xenotransplant. Methods: Transthoracic echocardiography (TTE) and right heart catheterizations were performed in the cardiac xenotransplant. Retrospective analysis of TTE and invasive hemodynamics were analyzed to assess correlation between various parameters. The following invasive hemodynamics were measured or calculated: right atrial pressure (RAP), pulmonary artery systolic and diastolic pressures (PASP, PADP), pulmonary vascular resistance (PVR), pulmonary artery pulsatility index (PAPi), cardiac output (CO), cardiac index (CI), right ventricular stroke work index (RVSWI) and cardiac power output (CPO). TTE measurements and calculations included: RAP based on inferior vena cava size and collapsibility, PASP calculated via tricuspid regurgitation velocity (TRV), PADP based on end diastolic pressure gradient, right ventricular outflow time-velocity integral (TVI RVOT), PVR (TRV/TVI RVOT x 10 +0.16) PAPi, CO (using left ventricular outflow tract (LVOT) velocity-time integral and LVOT area), CI (from TTE-derived CO), CPO and RVCPI {4x(TRV) 2 } x TAPSE as a surrogate of RVSWI. Results: Pearson correlation for RVSWI and RVCPI using invasive measurements obtained at the time of TTE was -0.095 and at time of mixed venous blood gas (mVBG) was 0.963. Mean absolute difference in time between mVBG and TTE was 4h 59 min. Pearson correlation for catheter-based continuous CO (CCO) monitoring with TTE was 0.965. Conclusions: In a retrospective analysis of porcine cardiac xenotransplant function, there was a strong correlation between directly measured hemodynamics with TTE, particularly when mVBG was obtained.
Abstract 10708: Dietary Methionine Restriction Protects Against Abdominal Aortic Aneurysm via Amino Acid Starvation Response
Authors: Li Yin, Takuro Shirasu, Yitao Huang, Eric W Kent, Mengxue Zhang, Nicholas Hoyt, Alexander C Gregg, Alessandra M Riccio, Lian-Wang Guo, Bowen Wang
Journal: Circulation (2022)

Introduction: Dietary intervention emerges as a promising non-medicinal avenue for the treatment of a wide range of diseases. Limiting the intake of single amino acid has been shown to produce health benefits similar to that of calorie restriction yet without significant risks of malnutrition. One of the established regimen, methionine restriction (MR), was recently shown to confer pleiotropic benefits in cardiometabolic disease models, largely attributed to the activation of the GCN2-mediated amino acid starvation response pathway. However, the therapeutic and mechanistic implications of dietary amino acid restriction remain unknown in abdominal aortic aneurysm (AAA), a lethal vascular disease that is without a cure other than the traumatic surgical repairs. Herein, we sought to probe the outcome of MR as well as the role of GCN2 in AAA. Methods and Results: Following a 2-week pre-treatment with MR (20% methionine level) or iso-caloric control diet, male Sprague Dawley rats were subjected to intraluminal elastase perfusion. At day 7, animals in the MR group showed significantly less aneurysmal dilation in comparison to control. To investigate the contribution from the GCN2-mediated amino acid starvation response, we subjected animals to the same dietary regimen of MR or control, followed by GCN2 silencing in the elastase-challenged aortic segments through localized infusion with GCN2-targeting or scrambled shRNA lentivirus. Indeed, tuning down aortic GCN2 effectively compromised the benefits exerted by MR against AAA. Finally, we determined whether GCN2 constitutes an intrinsic protector against aortic degeneration using GCN2 knockout mice ( Gcn2 -/- ). Following periaortic elastase challenge and β-aminopropionitrile treatment, Gcn2 -/- mice displayed exacerbated expansion of aneurysmal lesions in comparison to Gcn2 +/+ control mice at day 28 post procedure. Conclusions: Our study provides the first experimental evidence supporting a potential role of dietary amino acid restriction (e.g., MR) in the prevention of AAA development. Additionally, GCN2-mediated amino acid starvation response possibly underlies the anti-AAA benefit exerted by MR and serves as an intrinsic protector against AAA pathogenesis.
Abstract 10380: A Case of Statin-Induced Necrotizing Autoimmune Myopathy After Covid-19 Vaccination
Authors: Gagan Verma, Marta Arjonilla, Chad Gier, On Chen
Journal: Circulation (2022)

Introduction: Statins have become the most prescribed medications in the United States. We examine the case of a woman who developed statin induced necrotizing myopathy after receiving the Pfizer COVID-19 vaccine after 15 years of statin use. Case: A 67-year-old woman with history of hypothyroidism, hyperlipidemia, and a remote history of breast cancer, treated with surgical excision, presented with a two-month history of progressive proximal muscle weakness in all four extremities. During this time, she noticed unusual difficulty in her habitual exercise routine, culminating in being suddenly unable to walk or lift her arms. Prior to the onset of her symptoms, she reported that she had received the Pfizer COVID-19 booster vaccine. She had been adherent to her daily medications for over fifteen years (atorvastatin 20mg and levothyroxine 75mcg). Labs revealed creatine phosphokinase of 10,354. Muscle biopsy of the thigh was indicative of necrotizing myopathy. 3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were elevated at over 200 units, suggesting an immune-mediated myopathy. She was treated with intravenous immune globulin and placed on a prednisone taper. Her strength improved, and she was discharged home with physical therapy. Discussion: Statin-induced necrotizing autoimmune myopathy (SNAM) is a rare manifestation of autoimmune myositis. In the anti-HMG-CoA reductase subtype, the immune system is sensitized to HMG-CoA reductase resulting in immune-mediate cellular injury. The duration of exposure to statins prior to development of SNAM varies from 2 months to 10 years, with an average of 3 years. Our patient had previously been on statin therapy for 15 years without issue and subsequently developed SNAM after receiving a COVID-19 booster. This highlights the possibility that ribonucleotide vaccines, in particular COVID-19, may stimulate immune-mediated autoantibody formation and lead to increased risk for SNAM in patients on statin therapy. These patients would benefit from alternative lipid lowering therapies, such as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors.